DESCRIPTION: (Applicant's Description) The overall objective of this proposal is to conduct phase I and pharmacological studies of new anticancer agents. These studies will aim to define the recommended phase II dose, toxicities, pharmacokinetics, and pharmacodynamics of such agents. Some of these trials may incorporate pharmacokinetics or pharmacodynamic modulators. Five new s t udies are proposed. These include 1)evaluation of genotyping for abnormalities in the UGT*1.1 promoters region (known to cause Gilbert's syndrome) and phenotyping with buprenorphine (a known substrate for UGI*1.1) a s p o t e ntial predictors of CPT-11 toxicity (diarrhea) and SN-38 glucuronidation (known to be a substrate for UGT*1.1); 2) evaluation of [O]6-benzylguanine (BG) pharmacodynamics in patients with colorectal cancer or sarcoma undergoing surgical resections; 3)evaluation of BG in combination with temozolomide; 4)evaluation of ketoconazole (a potent inhibitor of CYP3A4 on carboxyanidoimadzole (a substrate for CYP3A4) pharmacokinetics and toxicity; and 5)evaluation of UCN-01 on biweekly (24 hr infusion) schedule. All studies will include both pharmacokinetics and correlative laboratory studies. The project total accrual is 375 patients, or 75 patients per year.